Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to temozolomide in human glioblastoma

O-Methylguanine DNA methyltransferase-positive glioblastoma tissues had a 67.7% rate of Gli1 nuclear staining.

• Higher Gli1 nuclear staining is associated with O-Methylguanine DNA methyltransferase-positive glioblastoma tissues compared to negative ones.
• Activation of the Hedgehog/Gli1 signaling pathway increases MGMT expression and reduces sensitivity to temozolomide treatment.
• Inhibiting Hedgehog/Gli1 signaling decreases MGMT expression and enhances sensitivity to temozolomide treatment.
• Changes in MGMT levels occur without altering the methylation status of the MGMT promoter.
• A potential Gli1 binding site was identified in the MGMT gene promoter region at -411 to -403 bp upstream of the transcriptional start site.
• The combination of cyclopamine and temozolomide shows a synergistic effect in inhibiting tumor growth in vivo.

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